Left ventricular dysfunction and cardiac arrhythmias are frequent in type 2 myotonic dystrophy: A case control study

doi:10.1016/j.nmd.2009.04.012

Neuromuscular Disorders

Volume 19, Issue 7, July 2009, Pages 468-472

https://doi.org/10.1016/j.nmd.2009.04.012 Get rights and content

Abstract

In contrast with Steinert’s disease (DM1), type 2 muscular dystrophy (DM2) is not known to be associated with a high prevalence of cardiac involvement. Our objective was to compare the results of detailed cardiac investigations in populations of DM2 and DM1 patients, and in controls.

Thirty-eight DM2 patients (17 males; age = 57.1 ± 15.2 years) were investigated for possible heart involvement, and their results compared with 76 age–sex matched DM1 patients and 76 controls. Cardiac abnormalities were present in 15 DM2 patients, including conductive defects in 14, systolic dysfunction in 6, supraventricular arrhythmias in 6 and stroke in 5 patients and were significantly more frequent than in controls. When compared to DM1 patients, conductive defects were less frequent, supraventricular arrhythmias had similar prevalence and there was a trend towards more frequent left ventricular dysfunction in DM2 patients. Our study suggests that systematic cardiac investigations should be recommended in these patients.

Introduction

Autosomal dominant neuromuscular disorders known as myotonic dystrophies are attributed to microsatellite repeat expansions [1], [2]. The nuclear accumulation of mutant RNA, which interferes with the splicing of multiple genes, may explain the involvement of multiple systems [3]. In most cases, the phenotype associates progressive myotonic myopathy, cataract, multiple endocrine organs dysfunction, respiratory insufficiency and heart disease [4].

DM1, or Steinert’s disease, and DM2, also called proximal myotonic myopathy, are two distinct types of myotonic dystrophies. Steinert’s disease is the most common (incidence 1/8000 population) neuromuscular disorder in adults, and is due to a CTG expansion in the DMPK gene [1]. DM2 is caused by a CCTG expansion in the ZNF9 gene [2]. Its 1/20,000 population incidence might be underestimated, since some patients have been misdiagnosed as suffering from DM1, or were simply unrecognized because of the subtle neuromuscular involvement and the complexity of the molecular genetic diagnosis.

The heart is involved in the majority of patients suffering from DM1, and a cardiac event is the primary cause of death in 20–29% of patients [5], [6]. In contrast, cardiac involvement is considered to be rare in DM2, but data regarding this population are sparse. A single study reported a series of 16 DM2 patients and did not support the possibility of major cardiac complications [7]. Conversely, several reports of isolated cases of conduction disturbances, pacemaker implantation and dilated cardiomyopathy have been reported [8], [9], [10], [11].

Hypothesizing that the severity of heart disease in DM2 may have been underestimated, we conducted this study to compare the prevalence of cardiac involvement in a large population of DM2 patients with matched DM1 patients and controls.

Section snippets

Study design

Patients with genetically proven DM2 who visited Pitié-Salpétriêre and Cochin Hospitals for routine evaluation from 2004 to December 2007 were included in our study. After providing informed consent, patients underwent neuromuscular, cardiac and respiratory investigations according to a predefined protocol. They were also screened for a history of heart disease among first or second degree relatives and only sudden death, heart failure due to non-ischemic dilated cardiomyopathy or pacemaker

Patient population (Tables 1 and 2)

Among 44 patients with genetically proven DM2, 1 declined to participate, and 5 patients were excluded because they presented specific cardiac disorders, including severe aortic stenosis associated with 3-vessel coronary artery disease in 1 patient, acute myocarditis in 1 patient and 2-vessel coronary disease in the 3 remaining patients. The results are therefore presented for 38 DM2 patients, 76 DM1 patients and 76 controls.

Southern blot quantification was not performed in 4 DM2 patients

Discussion

The main findings of our study are (1) a high prevalence of adverse cardiac events in patients presenting with DM2, when compared to controls, (2) an overall similar risk of cardiac involvement in DM2 and DM1 patients, with more frequent conductive disease in DM1 and a tendency to more frequent atrial fibrillation and left ventricular dysfunction in DM2 patients, and (3) an association between conduction system and depressed LVEF in DM2.

The strengths of our study are (1) the large population of

Limitations of the study

Despite being the largest study of patients suffering from DM2 reported thus far, the size of our patient population precluded detailed analyses of various subgroups. In our study, we report a high prevalence of overt cardiac involvement in DM2 patients. Our results are based on a strategy of systematic cardiac investigations that was planned previously. Although we assume that our strategy, while allowing earlier diagnosis and therapeutic, may favorably impact the prognostic of DM2 patients,

Funding sources

This study was supported by grants from the Association Française contre les Myopathies (AFM).

Acknowledgement

The authors do thank Professor Christian Spaulding for his assistance in the redaction of this manuscript.

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Left ventricular dysfunction and cardiac arrhythmias are frequent in type 2 myotonic dystrophy: A case control study

Abstract

Introduction

Section snippets

Study design

Patient population (Tables 1 and 2)

Discussion

Limitations of the study

Funding sources

Acknowledgement

Cell

J Neurol Sci

Neuromuscul Disord.

Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9

Science

Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues

J Cell Biol

Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum

Neurology

A 10-year study of mortality in a cohort of patients with myotonic dystrophy

Neurology